With the increasing use of microfluidics-based technologies in life sciences, the community is challenged with delivering customized and optimized prototypes at low cost and turn-around times. Current simulation- based design tools are computationally expensive (based on 3D multiphysics models) and are more suited for detailed analysis. In addition, conventional MEMS foundries are unable to meet the cost and time needs of research and development efforts for low volume manufacturing of custom microfluidic designs. We propose to develop and demonstrate a "Simulation Driven Microfabrication Methodology" to enable rapid design optimization and prototyping of microfluidic devices. From a library of standard and customized microfluidic components, the network (device) will be quickly assembled in a user-friendly GUI driven environment, and analyzed using a system solver based on a reduced order formulation. Algorithms for design and layout optimization with process and manufacturing constraints will be developed and integrated. In Phase I, the software will translate the optimized layout into bitmap-based images for rapid prototyping using a maskless photolithography technique. Proof-of-concept will be demonstrated by optimizing an enzymatic assay chip. In Phase II, we will enhance the modeling capabilities to address the diverse needs for microfluidic devices in genomic, proteomic, cell-based and diagnostic applications. Interfaces to other microfabrication processes will be developed. [unreadable] [unreadable] [unreadable]